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Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation
Journal article   Open access   Peer reviewed

Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation

Priscila Y. Sato, J. Kurt Chuprun, Laurel A. Grisanti, Meryl C. Woodall, Brett R. Brown, Rajika Roy, Christopher J. Traynham, Jessica Ibetti, Anna M. Lucchese, Ancai Yuan, …
Science signaling, v 11(560)
11 Dec 2018
PMID: 30538174
url
https://doi.org/10.1126/scisignal.aau0144View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

Biochemistry & Molecular Biology Cell Biology Life Sciences & Biomedicine Science & Technology
Increased abundance of GRK2 [G protein-coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser(670) is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes cell death. Here, we showed that mice with a S670A knock-in mutation in endogenous GRK2 showed reduced cardiomyocyte death and better cardiac function post-IR injury. Cultured GRK2-S670A knock-in cardiomyocytes subjected to IR in vitro showed enhanced glucose-mediated mitochondrial respiratory function that was partially due to maintenance of pyruvate dehydrogenase activity and improved glucose oxidation. Thus, we propose that mitochondrial GRK2 plays a detrimental role in cardiac glucose oxidation post-injury.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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